A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions
A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions
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DOI：
10.1242/jcs.03314
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Geiger, Benjamin
中科院分区：
文献类型：
--
作者：
Zaidel-Bar, Ronen;Milo, Ron;Geiger, Benjamin
不同的细胞过程由不同的整合素介导的粘附进行。细胞扩散和迁移由局灶性复合体驱动;由局灶性粘连驱动与细胞外基质的牢固粘附;以及由纤维粘连驱动基质重塑。调节这三种类型粘附的时空分布和动力学的机制尚不清楚。在这里，我们结合联合收割机活细胞成像，标记与磷酸特异性抗体和过表达的一种新的酪氨酸磷酸化桩蛋白突变体，以证明桩蛋白的酪氨酸磷酸化的调制调节的装配和营业额的粘附位点。此外，磷酸化的桩蛋白增强板状突起，而非磷酸化的桩蛋白是必不可少的纤维粘附形成和纤连蛋白fibrillogenesis。我们进一步表明，粘着斑激酶优先相互作用的酪氨酸磷酸化模拟桩蛋白和它的招聘涉及高营业额的焦点复合物和易位的焦点粘连。我们创建了一个数学模型，概括了所测量的动态的显着特征，并得出结论，衔接蛋白桩蛋白的酪氨酸磷酸化作为一个主要的开关，调节细胞的粘附表型。
Diverse cellular processes are carried out by distinct integrin-mediated adhesions. Cell spreading and migration are driven by focal complexes; robust adhesion to the extracellular matrix by focal adhesions; and matrix remodeling by fibrillar adhesions. The mechanism(s) regulating the spatio-temporal distribution and dynamics of the three types of adhesion are unknown. Here, we combine live-cell imaging, labeling with phosphospecific-antibodies and overexpression of a novel tyrosine phosphomimetic mutant of paxillin, to demonstrate that the modulation of tyrosine phosphorylation of paxillin regulates both the assembly and turnover of adhesion sites. Moreover, phosphorylated paxillin enhanced lamellipodial protrusions, whereas non-phosphorylated paxillin was essential for fibrillar adhesion formation and for fibronectin fibrillogenesis. We further show that focal adhesion kinase preferentially interacted with the tyrosine phosphomimetic paxillin and its recruitment is implicated in high turnover of focal complexes and translocation of focal adhesions. We created a mathematical model that recapitulates the salient features of the measured dynamics, and conclude that tyrosine phosphorylation of the adaptor protein paxillin functions as a major switch, regulating the adhesive phenotype of cells.